Recommended Workup for Suspected Postural Orthostatic Tachycardia Syndrome (POTS)
The diagnostic workup for suspected POTS should include heart rate assessment during positional change, with a heart rate increase ≥30 bpm (or ≥40 bpm in those 12-19 years) within 10 minutes of standing, absence of orthostatic hypotension, and symptoms of orthostatic intolerance for at least 3 months. 1
Initial Diagnostic Testing
Core Diagnostic Tests
Orthostatic Vital Sign Assessment:
- Active stand test (optimal diagnostic heart rate increase cutoff of 29 bpm)
- Tilt table test (optimal diagnostic heart rate increase cutoff of 38 bpm)
- Confirm absence of orthostatic hypotension (>20 mmHg reduction in systolic BP) 1
Basic Laboratory Testing:
- Complete blood count
- Basic metabolic panel
- Thyroid function tests
- Cardiac biomarkers (if cardiac injury suspected)
- Serum tryptase (baseline and during symptom flares if mast cell activation syndrome is suspected) 1
Expanded Evaluation for Atypical Presentations
For patients with "atypical" POTS features (older age at onset, male gender, prominent syncope, abnormal examination findings beyond joint hyperextensibility, or disease refractory to first-line treatments), an expanded workup is recommended 2:
Additional Cardiac Testing:
- ECG
- Echocardiogram
- Extended cardiac monitoring if arrhythmias suspected
Comprehensive Autonomic Testing:
- Quantitative sudomotor axon reflex test (QSART)
- Heart rate variability assessment
- Valsalva maneuver
Neuropathy Workup (if peripheral neuropathy suspected):
- Nerve conduction studies
- Skin biopsy for small fiber evaluation
Autoimmune Evaluation:
- Autoimmune panels
- Consider evaluation for Guillain-Barré syndrome if appropriate
Assessment for Associated Conditions
POTS has multiple potential etiologies and associated conditions that should be evaluated when clinically indicated 1:
Hypermobile Ehlers-Danlos Syndrome (hEDS):
- Joint hypermobility assessment using Beighton score
- Skin elasticity evaluation
Mast Cell Activation Syndrome (MCAS):
- Serum tryptase (baseline and during flares)
- 24-hour urine for N-methylhistamine, prostaglandin D2, or 11-beta-prostaglandin F2 alpha
Post-Viral Syndromes:
- Recent infection history (including COVID-19)
- Post-viral antibody testing when appropriate
Chronic Fatigue Syndrome:
- Fatigue severity assessment
- Post-exertional malaise evaluation
Follow-up Monitoring
- Laboratory monitoring every 3-6 months or when changing treatment regimens
- Immediate testing during significant symptom exacerbations
- Monitoring when starting medications that may affect electrolyte balance 1
Clinical Pitfalls and Considerations
- POTS is often misdiagnosed or has delayed diagnosis due to its heterogeneous presentation and overlap with other conditions
- Avoid universal testing in all patients with hypermobility disorders; instead use targeted testing based on clinical manifestations 1
- Consider SIH (Spontaneous Intracranial Hypotension) as a differential diagnosis in patients with orthostatic headaches 3
- Recognize that POTS pathophysiology is multifaceted and may include peripheral denervation, hypovolemia, venous pooling, and hyperadrenergic states 4
- Be aware that prolonged deconditioning can exacerbate POTS symptoms and should be addressed in management 4
By following this structured diagnostic approach, clinicians can effectively evaluate patients with suspected POTS, identify underlying mechanisms, and develop appropriate management strategies to improve patient outcomes.